The general goal of this research proposal is to use the barnacle muscle fiber as a preparation to elucidate the cellular mechanism underlying the toxic action of aluminum (A1(III)). The general working hypothesis is that A1(III) in the form of A1F (or more precisely A1(F)4) causes sustained stimulation of the ouabain- insensitive Na efflux as the result of persistent activation of the membrane adenylate cyclase system. Hypothesis also states that A1(III) reduces the size of the resting ouabain-insensitive Na efflux, and is able to interfere with one or more of the known mechanisms by which the ouabain-insensitive Na efflux is modulated. That is, at least 5 possibilities suggest themselves: first, that A1(III) in the absence of F- interferes with the cAMP- protein kinase-mediated response of the Na efflux. Second, that A1(III) interferes with the calmodulin/Ca2+-protein kinase- mediated response. Third, that A1(III) interferes with the phospholipid/Ca2+-mediated response. Fourth, that A1(III) (a) competes with Ca2+ for entry into the cell via the Ca2+ channel, and hence reduces the magnitude of the inward Ca2+ current following membrane depolarization, and (b) reduces the permeability of the plasmalemma to Na+ by displacing Ca2+ from superficial negative charges lying mainly on the outer side of the membrane, and from lipid phosphate groups. And fifth, that A1(III) reduces the magnitude of the stimulatory response of the Na efflux to acidification of the carbonium ion containing bathing medium. There are several distinct advantages to working with single barnacle muscle fibers: first, it is a relatively intact single cell preparation which by virtue of its size is ideal for microinjection experiments. Second, the kinetic results obtained with this preparation are straigthforward and considerably less ambiguous than the kinetics obtained with say, a tissue slice or a cell isolated with the aid of collagenase. Moreover, this approach permits any existing differences between fibers isolated from the same muscle bundle to be discerned. Third, much basic information regarding Na transport in this preparation is already available. And fourth, there is compelling evidence that the ouabain-insensitive Na efflux is modulated by several important kinases, notably cAMP-PK, CM/Ca2+-PK and PL/Ca2+-PKC (thus indicating that these systems are highly conserved), as well as a mechanism that is markedly sensitive to pCO2-carbonium ion changes. Studies of the effects of external acidification on Na and C1 movements in the presence of A1(III) may well have a direct bearing on the problem of acid rain and A1 cytotoxicity.